PROJECT SUMMARY Binaural hearing allows accurate and precise localization of sounds, and also confers advantages in complex environments such as workplaces, classrooms, restaurants, etc. where competing speech streams, noisy backgrounds, and reverberation abound. Unfortunately, an increasing population, spanning infancy through elderly and of diverse etiology, experiences severe difficulty in such environments despite having normal audiometric thresholds. Such difficulties are a hallmark of Central Auditory Processing Disorder, CAPD, which refers to difficulties in processing acoustic information in the central auditory system as demonstrated by poor hearing performance, often specifically in binaural hearing tasks. CAPD-like challenges can emerge as a result of temporary conductive hearing loss, aging, traumatic brain injury, autism, neurodegenerative diseases (multiple sclerosis) and use of bilateral clinical devices (hearing aids, cochlear implants). The consequences of CAPD can be severe; in children, CAPD impacts speech and language learning and academic performance and in adults, quality of life, job performance, fitness for duty, social interactions, etc. Regardless of etiology, a major limitation in CAPD is that clinical diagnosis is based on a cluster of symptoms, many of which overlap with other developmental disorders such as attention deficit hyperactivity disorder, learning disabilities and language deficits. Moreover, behavioral assessments of auditory processing, particularly in children and elderly, have poor reliability with scores often reflecting higher-level cognitive or analytical processes rather than basic auditory sensory processing. Thus, early intervention and implementation of rehabilitation strategies in CAPD patients is precluded. A potential way to surmount this barrier is to use non-invasive electrophysiological measures. Auditory brainstem responses (ABRs) are used worldwide for newborn and adult hearing screening. Because different ABR waves broadly represent activity within different parts of the auditory pathway, it is possible to assess the functional state of distinct stages of the pathway using appropriate stimuli. Binaural stages can be assessed using the binaural interaction component (BIC) of the ABR. The BIC is the residual ABR obtained after subtracting the sum of monaurally- from binaurally-evoked ABRs. Prior research has identified the BIC as a potential biomarker for binaural ability. As the BIC can be measured using equipment and methods already available in most audiology clinics, its development as diagnostic tool could have immediate and widespread clinical value. However, while comparative studies have reported robust BIC in a variety of model species, reports of human BIC are perplexingly variable and unreliable. The proposed research comprises three Aims to establish a comprehensive understanding of the BIC, including 1) identification of its brainstem circuit origin, 2) identification of sources of variability across mammalian species including humans, 3) identification of best practices in human BIC measurement, and assessment of the BIC as a biomarker for predicting meaningful aspects of human binaural perception.